Functional interaction with filamin A and intracellular Ca2+ enhance the surface membrane expression of a small-conductance Ca 2+-activated K+ (SK2) channel

Sassan Rafizadeh, Zheng Zhang, Ryan L. Woltz, Hyo Jeong Kim, Richard E. Myers, Ling Lu, Dipika Tuteja, Anil Singapuri, Amir Ali Ziaei Bigdeli, Sana Ben Harchache, Anne A Knowlton, Vladimir Yarov-Yarovoy, Ebenezer N. Yamoah, Nipavan Chiamvimonvat

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

For an excitable cell to function properly, a precise number of ion channel proteins need to be trafficked to distinct locations on the cell surface membrane, through a network and anchoring activity of cytoskeletal proteins. Not surprisingly, mutations in anchoring proteins have profound effects on membrane excitability. Ca2+- activated K+ channels (K Ca2 or SK) have been shown to play critical roles in shaping the cardiac atrial action potential profile. Here, we demonstrate that filamin A, a cytoskeletal protein, augments the trafficking of SK2 channels in cardiac myocytes. The trafficking of SK2 channel is Ca2+-dependent. Further, the Ca2+ dependence relies on another channel-interacting protein, α-actinin2, revealing a tight, yet intriguing, assembly of cytoskeletal proteins that orchestrate membrane expression of SK2 channels in cardiac myocytes. We assert that changes in SK channel trafficking would significantly alter atrial action potential and consequently atrial excitability. Identification of therapeutic targets to manipulate the subcellular localization of SK channels is likely to be clinically efficacious. The findings here may transcend the area of SK2 channel studies and may have implications not only in cardiac myocytes but in other types of excitable cells.

Original languageEnglish (US)
Pages (from-to)9989-9994
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number27
DOIs
StatePublished - Jul 8 2014

Keywords

  • Atrial fibrillation
  • Atrial myocytes
  • Ion channel trafficking

ASJC Scopus subject areas

  • General

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